Journal
METABOLISM-CLINICAL AND EXPERIMENTAL
Volume 62, Issue 11, Pages 1577-1586Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2013.07.002
Keywords
Metabolome; HCV; Oxidative stress; CE-TOFMS; Glutathione
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Funding
- Ministry of Health, Labor and Welfare of Japan
- Japan Science and Technology Agency
- Yamagata Prefectural Government and City of Tsuruoka
- Grants-in-Aid for Scientific Research [24590953, 23592784] Funding Source: KAKEN
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Objectives. Serum samples from patients with chronic hepatitis C were subjected to metabolomics analysis to clarify the pretreatment characteristics of their metabolites and also changes in specific metabolites resulting from antiviral therapy with pegylated interferon plus ribavirin (PegIFN/RBV). Materials/Methods. The serum levels of low-molecular-weight metabolites in the twenty patients before and 24 weeks after completion of PegIFN/RBV therapy were analyzed using capillary electrophoresis and liquid chromatography-mass spectrometry. Results. Ten patients showed a non-virological response (NVR) and 10 achieved a sustained virological response (SVR) with eradication of viremia. The pretreatment levels of tryptophan were significantly higher in the patients of SVR than in those of NVR (p = 0.010). The area under the curve (AUC) value of tryptophan calculated from the receiver operating characteristic (ROC) curve for discriminating SVR from NVR was 0.84 (95% confidential interval, 0.66-1.02, p = 0.010). The ROC curve of multiple logistic regression model incorporating the pretreatment levels of tryptophan and gamma-glutamate-arginine showed that the AUC value was highly significant (AUC = 0.92, 95% confidential interval, 0.79-1.05, p = 0.002). Twenty four weeks after completion of treatment, the levels of,gamma-glutamyl dipeptides, glutamic acid, 5-oxoproline, glucosamine and methionine sulfoxide were decreased, whereas those of 5-methoxy-3-indoleacetate, glutamine, kynurenine and lysine were increased significantly (p < 0.05) in both the NVR and SVR patients. Conclusions. The pretreatment serum levels of certain metabolites including tryptophan are associated with the response to PegIFN/RBV therapy. PegIFN/RBV therapy can ameliorate the oxidative stress responsible for glutathione metabolism. (C) 2013 Elsevier Inc. All rights reserved.
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